{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T01:25:48Z","timestamp":1777771548145,"version":"3.51.4"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background and objective<\/jats:title>\n<jats:p>A cytokine storm is caused by inflammatory cells, including pro-inflammatory macrophage phenotype (M1), and play a critical role in the pathogenesis of COVID-19, in which diffuse alveolar damage occurs in the lungs due to oxidative stress exposure. Heme oxygenase (HO)-1 is a stress-induced protein produced by the anti-inflammatory \/ anti-oxidative macrophage phenotype (M2), which also produces soluble CD163 (sCD163). In our study, we investigated and determined that serum HO-1 can be a predictive biomarker for assessing both the severity and the outcome of COVID-19 patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>The serum concentrations of HO-1 and sCD163 of COVID-19 patients were measured on admission. The relationship between these biomarkers and other clinical parameters and outcomes were evaluated.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Sixty-four COVID-19 patients (11 mild, 38 moderate, and 15 severe cases) were assessed. The serum HO-1 tended to increase (11.0 ng\/mL vs. 24.3 ng\/mL vs. 59.6 ng\/mL with severity). Serum HO-1 correlated with serum lactate dehydrogenase (R = 0.422), C-reactive protein (R = 0.463), and the ground glass opacity (GGO) and consolidation score (R = 0.625) of chest computed tomography. The serum HO-1 showed a better area under the curve (AUC) for predicting ICU admission than the serum sCD163 (HO-1; 0.816 and sCD163; 0.743). In addition, composite parameters including serum HO-1 and the GGO and consolidation score showed a higher AUC for predicting ICU admission than the AUC of a single parameter.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Clinically, serum HO-1, reflecting the activation of M2, could be a very useful marker for evaluating disease severity and predicting prognoses for COVID-19 patients. In addition, controlling activated M2 might be a preventative COVID-19 therapeutic target.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0273500","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T17:34:02Z","timestamp":1661362442000},"page":"e0273500","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Heme oxygenase-1 as an important predictor of the severity of COVID-19"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2574-2516","authenticated-orcid":true,"given":"Yu","family":"Hara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1578-3226","authenticated-orcid":true,"given":"Jun","family":"Tsukiji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Yabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshika","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruka","family":"Hirose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Ebina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"pone.0273500.ref001","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"C Huang","year":"2020","journal-title":"Lancet"},{"key":"pone.0273500.ref002","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S1473-3099(20)30243-7","article-title":"Estimates of the severity of coronavirus disease 2019: a model-based analysis","volume":"20","author":"R Verity","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"pone.0273500.ref003","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"N Chen","year":"2020","journal-title":"Lancet"},{"key":"pone.0273500.ref004","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.chest.2020.04.010","article-title":"Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China","volume":"158","author":"Medical Treatment Expert Group for COVID-19","year":"2020","journal-title":"Chest"},{"key":"pone.0273500.ref005","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"China Medical Treatment Expert Group for Covid-19. 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